Objective To study the effect of NF?E2 related factor 2 (Nrf?2) pathway activation on particulate matter 2. 5 (PM_2.5 )?induced reproduction injury in female rats. Methods Thirty Sprague Dawley rats were randomly divided into control (normal saline), low dose exposure (1. 5 mg/ kg PM_2.5 ), and high dose exposure (37. 5 mg/ kg PM_2.5) groups. The levels of tumor necrosis factor?α (TNF?α), interleukin 1?β (IL?1β), and interleukin?6 (IL?6) were measured by enzyme?linked immunosorbent assay. The mRNA and protein expression of Nrf?2 and heme oxygenase?1 (HO?1) were also examined by qPCR and western blot. Results There was a significant increase in TNF?α, IL?1β, and IL?6 expression in the low dose and high dose exposure groups compared with the control groups ( P < 0. 05). The expression levels were also increased with increasing dose of PM_2.5 (r = 0. 870, 0. 847, and 0. 855, respectively). Both the Mrna and protein expressions of Nrf?2 and HO?1 were also significantly increased in the low dose and high dose exposure groups compared with controls ( P <0. 05). Conclusions The Nrf?2 signaling pathway is activated following exposure of PM2. 5 in female rats, although PM2. 5 can still induce uterine inflammation and injury.