Aim To investigate the protective effect and mechanism of procyanidin B₂ (PCB₂) on lipopolysaccharide (LPS)-induced cardiomyocyte injury. Methods Cardiomyocytes H9c2 were cultured normally, and induced by LPS to establish cell damage models. The model cells were treated with PCB₂ of 6.5,2.5 and 25.0 μmol/L, 25.0 μmol/L PCB₂ treatment model was then treated with NF-κB signaling pathway inhibitor PDTC treatment. Tetrazolium salt colorimetry (MTT) was used to detect cell survival; flow cytometry was used to detect cell apoptosis; enzyme-linked immunosorbent assay (ELISA) was used to detect cell tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels; malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) kits were used to detect MDA content and activity of SOD and GSH-Px, respectively; Western blot was used to detect the expression of nuclear factor-κB (NF-κB) and IκB-α in cells. Results Compared with control group, the cell survival rate of the LPS group was significantly reduced (P＜0.05); compared with LPS group, PCB₂ significantly increased the cell survival rate (P＜0.05). Compared with control group, the apoptosis rate was significantly increased in LPS group (P＜0.05); compared with LPS group, PCB₂ significantly reduced the apoptosis rate (P＜0.05). Compared with control group, the levels of TNF-α, IL-1β, and were significantly increased IL-6 in LPS group (P＜0.05); compared with LPS group, PCB₂ significantly reduced the levels of TNF-α, IL-1β, and IL-6 in the cells (P＜0.05). Compared with control group, the cell MDA content in LPS group was significantly increased, and the SOD and GSH-Px activities were significantly reduced (P＜0.05); compared with LPS group, PCB₂ significantly reduced the cellular MDA content and significantly increased the SOD and GSH-Px activities (P＜0.05). Compared with control group, the cell NF-κB protein expression in LPS group was significantly increased, and the IκB-α protein expression was significantly decreased (P＜0.05); compared with LPS group, PCB₂ significantly reduced the cell NF-κB protein expression and significantly increased IκB- α protein expression (P＜0.05). Compared with LPS+PCB₂ group, LPS+PCB₂₊PDTC significantly reduced the apoptosis rate, TNF-α, IL-1β, IL-6 and MDA content, and significantly increased the SOD and GSH-Px activities. Conclusion PCB₂ reduces the apoptosis rate, inflammation level and oxidative stress of cardiomyocytes induced by LPS, and improves cell survival rate, which may be related to inhibiting the activation of NF-κB signaling pathway.