Aim To investigate the effect and possible mechanism of oxymatrine injection (OMT) on cardiac function and ventricular remodeling in doxorubicin-induced chronic heart failure (CHF) rats. Methods The rat model with CHF was established by intraperitoneal injection (ip) of adriamycin (1.5 mg/kg, twice a week for 6 weeks).The model group, captopril injection (CTP, 6.5 mg/kg) group and OMT low (25 mg/kg), medium (50 mg/kg), high (100 mg/kg) dose group were set up, and the control group was set up, with 10 rats in each group. The rats in each group were treated by intraperitoneal injection once a day. 4 weeks later, the cardiac function indexes (left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular fractional shortening (LVFS), stroke volume (SV)) were measured through animal ultrasound; the content of cardiac troponin I (cTnI), brain natriuretic peptide (BNP), stromelysin-2 (ST2) in serum were detected by enzyme-linked immunosorbent assay (ELISA); the left ventricular hypertrophy index (LVHI) was calculated; the morphological changes and fibrosis of myocardial tissue were observed by HE staining and Masson staining; the expression of collagen I (Coll-1), α smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), Smad2, p-Smad2, Smad3, p-Smad3, Smad7 were detected by Western blot. Results Compared with the model group, the LVESD and LVEDD were decreased in CTP group and OMT low, medium, high dose groups; the LVFS, LVEF and SV were increased (all P＜0.05). The contents of cTnI, BNP and ST2 were decreased (all P＜0.05). The pathological changes and fibrosis of myocardial tissue were significantly improved, and the collagen volume fraction (CVF) were decreased (P＜0.05). The expressions of Coll-1, α-SMA and TGF-β1 were decreased; the ratio of p-Smad2/Smad2 and p-Smad3/Smad3 were decreased; the expression of Smad7 were increased (all P＜0.05). The effect of OMT on various indexes of CHF rats were dose-dependent, and the effect of OMT high-dose group on various indexes were significantly better than those of CTP group. Conclusion OMT can improve cardiac function and inhibit ventricular remodeling in CHF rats, which mechanism may be related to the inhibition of TGF-β1/Smads signaling pathway.