Objective：To investigate the therapeutics effect and the potential mechanism of paeoniflorin on the bleomycin-induced pulmonary fibrosis in mice. Methods：Sixty adult male SPF C57BL/6 mice were randomly divided into four groups：the control group (Sham operation，SH)，the control+paeoniflorin group (SH+PA)，the bleomycin group (BLM) and the bleomycin+paeoniflorin group (BLM+PA). From the day of operation，the mice of the SH+PA and BLM+PA groups were treated with paeoniflorin intragastrically (50 mg/kg，daily) while the mice of the SH and BLM groups were given the same volume of normal saline. The model of pulmonary fibrosis was established through intratracheally instillation with bleomycin (2 mg/kg) except for the control group，in which normal saline was used. All the samples were sacrificed on the day 14 after operation，and the change of body weight and mortality rates of each group were analyzed. The pathological section of lung tissues were harvested for hemotoxylin and eosin stain. Collagen deposition in the lung was determined by measuring the total hydroxyproline content. ELISA was performed to analyze the level of IL-18 and IL-1β in the lung homogenates. The levels of NLRP3 and TGF-β1 in the lung were detected by Western blotting. Results：Paeoniflorin significantly increased the survival rate and attenuated the collagen deposition in the bleomycin-induced pulmonary fibrosis mouse model compared with the control group (P＜0.05). The IL-18 and IL-1β in the lung homogenates were decreased notably after administration of paeoniflorin，when compared to the control group (P＜0.05). The expression of NLRP3 and TGF-β1 were down regulated significantly (P＜0.05). Conclusion：Paeoniflorin may attenuate bleomycin-induced pulmonary fibrosis in mice by suppressing NLRP3 inflammsome formation.