By constructing the theoretical hypothesis that the transportation infrastructure affects the commercial circulation efficiency, using the interprovincial panel data from 2000 to 2020, this paper empirically analyzes the effect and mechanism of transportation infrastructure on commercial circulation efficiency. The results show that: (1) transportation infrastructure can significantly promote the efficiency of wholesale and retail circulation, both the robustness test of substitution variables and the test of instrumental variables supported the benchmark estimation results. (2) The effect of transportation infrastructure on commercial circulation efficiency is different in space and time, the effect in inland area was significantly greater than that in coastal area, and the influence effect after the opening of EMU is significantly greater than that before the EMU is in operation. (3) The mediation effect estimation results show that, transportation infrastructure significantly enhances the efficiency of wholesale and retail industries through three mechanisms of cost savings, market size expansion and division of labor deepening.