In order to apply microwave irradiation (MW) in the wet blue bating process, the influence of different heating methods on 537 acid protease enzyme activity and enzymatic reaction was investigated at first, and then the effect of MW on wet blue bating process was also studied through measuring the spent component, grain morphology and leather mechanical properties. The results showed that MW had a negative effect on enzyme activity and rate of enzymatic reaction but had a positive effect on the affinity between enzyme and substrate. In the wet blue bating process under MW, there was less collagen hydrolyzed and the content of chromium releasing was only 45.54% compared with water bath heating; in addition, the shrinkage temperature, softness and tensile strength were also improved. Moreover, the bated wet blue under MW had flatter grain and stretched pores. In short, microwave irradiation could not only accelerate the rate but also improve the effect of wet blue bating process. Therefore, it would be a fast and cleaner method for leather making.