This study aimed to investigate the preventive effect of isostrictiniin (ISO) from Nymphaea candida against CCl4-induced hepatic fibrosis (HF) in mice. HF in mice was induced by intraperitoneally injecting 10% CCl4 olive oil solution twice a week. After intragastric administration for 8 weeks. ISO (25, 50, or 100mg/kg) could significantly reduce the serum AST, ALT, ALP, HA, LN, PC-III, C-IV, IL-1 beta, and TNF-alpha levels in HF mice, and the collagen fiber deposition in ISO group was significantly less than that in the model group. Compared with control group, the protein expression of IKK alpha, NF-kappa B p65, p-NF-kappa KB p65, p-I kappa B alpha in model group were increased as well as the relative content of IKK alpha, NF-kappa B p65, and I kappa B alpha mRNA. ISO could reverse the expression of these relative proteins and mRNA in HF mice. Our findings confirm that ISO has anti-HF activity, and its mechanism is related to the regulation of NF-kappa B pathway. [GRAPHICS]