Abstract: The spatial DUBIN panel model was built based on the panel data from 2005 to 2015 of 30 provincial-level economic units in China. Based on the geographic weight matrix and economic weight matrix, the direct and indirect effects of environmental regulation on eco-efficiency were studied. The results showed that the total effect regression coefficients of environmental regulation under the two spatial weight matrixes were 0.039 4 and 0.045 5 respectively, and the indirect effect regression coefficients were 0.004 7 and 0.028 7 respectively. The coefficient test was significant and had a positive effect on improving regional ecological efficiency, but the direct effect regression coefficients were not significant; the environmental regulations of regions with similar geography and economic development level had profound mutual influence. Ignoring the spillover effects of environmental regulation might lead to biased conclusions. The proportion of the tertiary industry, the proportion of state-owned enterprises, the proportion of foreign investment and the improvement of R&D intensity all play an active role in enhancing ecological efficiency. Increasing the proportion of capital labor and trade openness is not conducive to raising the level of ecological efficiency.