Objective To investigate the effect of solasonine (SS) on myocardial fibrosis induced by pressure overload in mice. Methods Aortic banding (AB) was used to construct a mice model of myocardial fibrosis. A total of 40 male C57/B6 mice (8-10 weeks) were randomly divided into sham-operated group, sham-operated+SS group, AB group, AB+SS group (n=10 each). 3 weeks after AB surgery, AB+SS group was intraperitoneally injected with SS (10mg/kg) every day, AB group was intraperitoneally injected with an equal amount of normal saline every day. 3 weeks after sham operation, sham-operated+SS group was intraperitoneally injected with SS (10mg/kg) every day, sham-operated group was intraperitoneally injected with an equal amount of normal saline every day. After intraperitoneal injection for 1 week, the cardiac function of mice in each group was detected by cardiac ultrasound and heart tissues were collected. Picrosirius red staining were used to observe cardiac fibrosis，and qPCR was used to detect the mRNA levels of fibrosis markers. Western blot was used to detect the related signaling pathways. Phosphate buffer saline (PBS), PBS+SB203580 (p38 MAPK inhibitor), PBS+SS, TGF-β1, TGF-β1+SB203580, TGF-β1+SS were added to the primary cultured rat fibroblasts. Cells were collected after 24h for subsequent detection. Results In this study, the mouse model of myocardial fibrosis was successfully established. Compared with AB group, the levels of LVEF and LVFS in AB+SS group were significantly increased (P＜0.05), while the levels of LVEDD were significantly decreased (P＜0.05). The level of interstitial and perivascular collagen deposition in AB+SS group was higher than AB group (P＜0.05), and the mRNA relative levels of Col-1, Col-3 and TGFβ in AB+SS group were significantly lower than those in AB group (P＜0.05). The phosphorylation level of p38 MAPK in AB+SS group was lower than that in AB group (P＜0.05). The results of in vitro cell experiments showed that the mRNA levels of COL-1, COL-3 and TGF-β in the SB203580 and SS groups were significantly lower than those in the ISO group (P＜0.05). Conclusion SS can inhibit the phosphorylation of p38 MAPK and then improve the myocardial fibrosis induced by pressure overload.