Objective To establish a trimethyltin chloride (TMT) -induced learning and memory impairment model in rats, and to investigate the protective effects and potential mechanisms of ferulic acid. Methods Specific pathogen-free male SD rats were randomly divided into control group, TMT intoxication group, fluoxetine group and 25, 50, 100 mg/kg ferulic acid group. The rats in the last five groups were injected with a dose of 8 mg/kg body weight TMT solution, and the rats in control group were injected with the same volume of 0.9% sodium chloride solution. After 24 hours of TMT injection, the rats in fluoxetine group were treated 10 mg/kg body weight of fluoxetine, the rats in the three ferulic acid groups were treated with ferulic acid at doses of 25, 50, and 100 mg/kg body weight, respectively. The rats in the control group and TMT intoxication group were treated with the same volume of 0.9% sodium chloride solution, once per day for continuous gavage for 28 days. Morris water maze experiment and light-dark box test were used to assess the learning and memory abilities of the rats. The mRNA and protein expressions of nuclear transcription factor-κB (NF-κB), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the rat hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the rat hippocampus were detected by enzyme-linked immunosorbent assay. Results Compared with the control group, rats of TMT intoxication group on day four had prolonged escape latency (P<0.05), fewer platform crossing (P<0.05), shorter time spent in the target quadrant and shorter latency to enter the dark compartment (all P<0.05). The mRNA and protein relative expression of NF-κB, TNF-α and IL-1β increased (all P<0.05), ROS and MDA levels increased (all P<0.05), SOD and CAT activities decreased (all P<0.05) in the rat hippocampus of TMT intoxication group on day four compared with that of the control group. Except for the terms of escape latency and target quadrant period of the rats in the 25 mg/kg ferulic acid group, rats in three ferulic acid groups on day four had lower escape latency (all P<0.05), more platform crossing (all P<0.05), longer period in the target quadrant and longer latency to enter the dark compartment (all P<0.05), compared with TMT intoxication group. Except for the relative protein expression of TNF-α in the rats of 50 mg/kg ferulic acid group, the mRNA and protein expression of NF-κB, TNF-α and IL-1β decreased (all P<0.05), ROS and MDA levels were reduced (all P<0.05), and the activities of SOD and CAT increased (all P<0.05) in the hippocampus of rats of 50 and 100 mg/kg ferulic acid groups compared with TMT intoxication group. Conclusion Ferulic acid can reverse TMT-induced learning and memory impairment in rats, and its mechanism of action may be related to alleviating oxidative stress damage and excessive inflammatory response in rat hippocampus.