OBJECTIVE： To investigate the protective effect and its mechanism of thymoquinone （TQ） on myocardial fibrosis （MF） induced by lipopolysaccharide in rats. METHODS： Totally 40 male Wistar rats were randomly divided into control group， model group， TQ low-dose and high-dose groups [5， 10 mg/（kg?d）]， with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally， other groups were given LPS intraperitoneally to induce MF model， once a day， for consecutive 3 weeks. Since the first day of modeling， administration group was given relevant medicine intraperitoneally， once a day， for consecutive 3 weeks. After last medication， ELISA method was used to detect the contents of serum inflammation factors （IL-1β， IL-6， TNF-α） in rats. Cardiac mass parameters （HW/BM， LVW/BW） were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators （MDA， SOD） and myocardial collagen indexes （HYP， Col-Ⅰ， Col-Ⅲ） were detected by chemical analysis， xanthine oxidase method or ELISA. mRNA expression of regulation genes （Col-Ⅰ， Col-Ⅲ， MMP-3， MMP-9， TGF-β1 and Smad3） related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS： Compared with control group， there were swollen myocardial cells， disordered nuclei of different sizes and visible fiber hyperplasia in model group； the levels of serum inflammatory factors and LVW/BW， cardiac contents of MDA， HYP， Col-Ⅰand Col-Ⅲ， mRNA expression of Col-Ⅲ， TGF-β1 and Smad3 in model group were increased significantly （P＜0.05）， while SOD activity was decreased significantly （P＜0.05）. Compared with model group， the degree of myocardial fibrosis was improved in TQ groups to different extents； serum content of IL-1β and the contents of MDA， HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group， serum contents of IL-1β， IL-6 and TNF-α， LVW/BW and the contents of MDA， HYP， Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ， Col -Ⅲ， TGF-β1 in TQ groups were decreased significantly （P＜0.05）. The activities of SOD in cardiac tissue were increased significantly in TQ groups （P＜0.05）. There was no statistical significance in other indexes among groups （P＞0.05）. CONCLUSIONS： TQ can protect against MF model rats to certain extent， the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction， and down-regulation of mRNA expression of Col-Ⅰ， Col-Ⅲ and TGF-β1.