【Abstract】 Objective To explore the effect and mechanism of alkannin on bleomycin induced pulmonary fibrosis in mice. Methods 20 SPF mice of 8-10 weeks old were divided into treatment group (intraperitoneal injection of shikonin), control group (intraperitoneal injection of alkannin after intraperitoneal injection of normal saline of the same dose) and treatment group (tail vein injection of schampk lentivirus agent on the basis of treatment of treatment group) , model group (no processing). The control group was given the same dose of saline intraperitoneally. The degree of pulmonary fibrosis was evaluated by detecting the content of collagen, HE staining and Masson staining. The protein levels of NOX4, CollagenI and α-SMA were detected by Western blot. The mechanism of bleomycin induced pulmonary fibrosis was explored by SiRNA silences AMPK gene. Results Compared with the control group, the content of collagen, urinary protein, inflammatory cell infiltration and interstitial fibrosis in the model group were significantly increased (P＜0.05). Compared with the model group, the content of collagen proteinuria, inflammatory cell infiltration and interstitial fibrosis in the lung of the treatment group were significantly lower (P＜0.05). Compared with the control group, the optical density of NOX4, P Smad3 and α SMA in the lung tissue of the model group was significantly increased (P＜0.05), while the expression of the above proteins in the treatment group was significantly inhibited (P＜0.05). The results of Western blot showed that NOX4 and extracellular matrix (collagen I, α-SMA) were abundantly expressed in the lung tissue of the model group, but the expression of the above protein molecules in the treatment group was significantly inhibited (P＜0.05). In the control group, alkannin did not affect the expression of NOX4, collagenani and α-SMA. Compared with the control group, the expression of NOX4, CollagenI and α-SMA in the lung tissue of the model group was significantly increased, while the expression of P AMPK was decreased (P＜0.05). The expression of NOX4, collagenani, α-SMA and the expression of P AMPK in the lung tissue of the treated group were decreased. The inhibition of NOX4, collagenani and α SMA expression was relieved in the treatment intervention group, and the increase of P AMPK expression was inhibited by alkannin (P＜0.05). Conclusion Alkannin can inhibit the expression of NOX4 through AMPK, so as to reduce bleomycin induced pulmonary fibrosis in mice.