A self-healing anti-corrosion coating based on small-size hexamethylene diisocyanate (HDI) microcapsules was prepared, which can improve the corrosion resistance of the coating and realize the on-line repair of coating scratch defects. This paper attempts to adjust the amount of emulsifier (from 0% to 5%), stirring rate (from 300 r/min to 700 r/min), and system pH value (from 2.5 to 4.5) in the process of synthesizing HDI microcapsules by interfacial polymerization, reduce the average particle size of microcapsules, and characterize the structure and thermal stability of microcapsules by core dyeing experiment, Flight Test Instrumentation Requirements (FTIR), and Thermogravimetric Analysis (TG). Through high-speed physical mixing, HDI microcapsules were added into epoxy resin matrix to prepare self-healing coating. The effects of HDI microcapsules on the basic mechanical properties and corrosion resistance of the coating were studied by universal tensile machine, pull-out tester, and Electrochemical Impedance Spectroscopy (EIS). In addition, the internal self-healing mechanism and self-healing ability of various composite coatings in 3.5wt.% NaCl solution were analyzed combined with Wire Beam Electrode (WBE) test and scratch coating immersion corrosion experiment. Particle size analysis of oil in water emulsion system and microcapsules morphology observation results under different reaction conditions indicated that the optimum emulsifier sodium dodecyl benzene sulfonate addition in the preparation of microcapsules was 3%, the stirring rate was 600 r/min, and the pH value of the system was 3.5. At this time, the average particle size of microcapsules was reduced to 59 μm and the molding rate reached 82%. HDI microcapsules have regular spherical structure and dense surface with certain roughness. The core dyeing experiment and FTIR showed that the microcapsule was composed of urea formaldehyde resin shell and HDI core. TG analysis revealed that the initial decomposition temperature of microcapsules with desirable thermal stability was 260 ℃, and the end decomposition temperature was 540 ℃. Along with the increase of HDI microcapsule content from 0% to 10%, the tensile strength of self-healing coating reduced from 53.24 MPa to 24.61 MPa, and the adhesion gradually decreased from 10.3 MPa to 3.9 MPa. After immersion in 3.5wt.% NaCl solution for 144 h, the fitting impedances Rp of self-healing coatings containing 0%, 1%, 5%, and 10% microcapsules were 1.5×108 Ω/cm2, 2.2×108 Ω/cm2, 3.7×108 Ω/cm2, and 2.8×108 Ω/cm2 respectively. According to WBE test and immersion corrosion test, the composite coating with 5% microcapsule content has the best self-healing performance, and the maximum corrosion current in the coating scratch position was suppressed from 4.8×10?7 A to 2.5×10?7 A. The Scanning Electron Microscope (SEM) photographs demonstrated that the coating scratch basically heals after 36 h immersion by the polyurethane repair materials. In conclusion, when HDI microcapsules prepared by optimized interfacial polymerization are evenly dispersed into the coating, the microcapsules improve the corrosion resistance of the coating through coordinated barrier effect. Meanwhile, the microcapsules in the self-healing coating release the core HDI at the damaged position, and quickly react with the corrosive solution to heal the scratch defects of the coating in a short period of time.