Shaofu Zhuyu Decoction (SZD) exhibited significant anti-inflammation and analgesic effect, which is considered for alleviating endometriosis. However, the therapeutic mechanisms of SZD still need comprehensive investigation. In this study, we performed a combined analysis of proteomics and metabolism to elucidate the potential mechanism underlying the effect of SZD on endometriosis-associated dysmenorrhea in mice. The size of ectopic focus in endometriosis model mice was dramatically decreased by SZD in high-dose for two-weeks. Many proinflammatory responsive cytokines were stimulated in endometriosis model mice and depressed by SZD, including TNF-, PGE2 and IL-6. Proteomics analysis suggest there are 636 up-regulated and 239 down-regulated differentially expressed proteins (DEPs) in comparison of model vs control, and SZD in high dose (HT) vs model, respectively. We found there are 44 overlapped DEPs in comparisons of model vs control with upregulation, HT vs control with upregulation and HT vs model with d