〔Abstract〕 Objective To study the expression changes of LncRNA-MEG3 in the process of rat cardiac fibrosis and cardiac fibroblasts(CFs) activation and proliferation. Methods SD rats were subcutaneously injected with isoproterenol(ISO) into the abdomen to construct a myocardial fibrosis animal model as the experimental group(ISO group),and the control group was injected with the same amount of normal saline; the CFs of suckling rats were extracted, and transforming growth factor β1(TGF-β1) was used to construct a cell-level fibrosis model as the experimental group(TGF-β1 group),and the control group was CFs cultured normally without TGF-β1;HE and Masson staining were used to observe the changes of myocardial tissue collagen; Western blot method was used to detect the expression of α-smooth muscle actin(α-SMA) and collagen type I(Collagen I) protein; qRT-PCR method was used to detect the expression of Collagen I,α-SMA mRNA and MEG3;The CCK-8 method was used to detect the absorbance(OD value) of CFs after TGF-β1 was used. Results The results of HE and Masson staining indicated that compared with the control group, the volume of cardiomyocytes in the ISO group became larger and disordered, and the area of tissue collagen increased significantly.Compared with the control group, Collagen I,α-SMA protein and mRNA expression in ISO group and TGF-β1 group increased significantly, and the expression of LncRNA-MEG3 decreased significantly; The results of CCK-8 experiments suggested that CFs stimulated by TGF-β1 for 24 h and 48 h significantly increased the OD value of cells compared with the control group, that is, the cell proliferation activity enhanced. Conclusion The expression of LncRNA-MEG3 in rat myocardial fibrosis tissue and the activation and proliferation of CFs cells significantly reduced, suggesting that MEG3 may play a negative regulatory role in rat myocardial fibrosis and activation and proliferation of CFs, providing new ideas for clinical myocardial fibrosis prevention and research.