Aim To investigate the mechanism of high sodium salt induced proliferation of cardiac fibroblasts (CFs) and the intervention effect of dendrobine. Methods Rat CFs were cultured with tissue explant method in vitro.The experiments were divided into 3 groups:control group (containing 139 mmol/L Na＋), high sodium salt group (containing 161 mmol/L Na＋), dendrobine group (161 mmol/L Na＋＋10－5 mol/L dendrobine), and cells were cultured for 48 hours. CCK-8 cell proliferation kit and MTT colorimetric assay were used to detect the proliferation of cells in each group.The protein expressions of proliferating cell nuclear antigen (PCNA), phosphorylated extracellular regulated protein kinase 1/2 (p-ERK1/2) and phosphorylated nuclear factor κB p65 (p-NF-κB p65) were detected by Western blot assay. The mRNA expressions of monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by real-time fluorescence quantitative PCR. Results Compared with the control group, the proliferations of CFs in the high sodium salt group were significantly increased after 48 hours culture. Compared with the high sodium salt group, 10－5 mol/L dendrobine could significantly inhibit the proliferation of CFs. Compared with the control group, the protein expressions of p-ERK1/2 and p-NF-κB p65 were increased, inflammatory factors MCP-1, VCAM-1 and ICAM-1 mRNA expressions were increased in high sodium salt group. Compared with the high sodium salt group, dendrobine could significantly reduce the expressions of PCNA and p-NF-κB p65 proteins and the expression of MCP-1 mRNA, but had no significant effect on the expressions of p-ERK1/2, VCAM-1 and ICAM-1. Conclusion High sodium salt induces the proliferation of CFs and the expression of inflammatory factors, and its mechanism is related to the upregulation of p-ERK1/2 and p-NF-κB p65 expressions. Dendrobine inhibits these effects and its mechanism is related to the inhibition of p-NF-κB p65.