Introduction: Maternal stress during pregnancy leads to neuroinflammation of the fetus and cognitive disorders in children. On the other side, Trichostatin A (TSA) as a histone deacetylase inhibitor has anti-inflammatory and neuroprotective effects. The aim of the present study was an evaluation of TSA effect on amelioration of spatial memory deficit and modification of pro-inflammatory cytokines in rat’s hippocampus of prenatal footshock stress model. Methods: In the present study, 24 pregnant Wistar rats were divided into 4 groups including control, PFS+Saline, PFS+TSA5, and PFS+TSA10. In order to induce prenatal footshock stress (PFS), the pregnant rats were subjected to electrical shock at 1 mA, 50 Hz for 2 seconds with 5 repetitions at 3-minute intervals from 12 to 18 days of pregnancy. Two hours before applying the shock intraperitoneal administration of TSA was performed daily. When the offsprings were one-month old, their spatial memory was assessed by the Morris water maze. Finally, the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured by ELISA method. Results: a reduction in spatial memory and an increase in the level of TNF-α, IL-1β, and IL-6 were observed in PFS+Saline group compared to the control. Besides, spatial learning showed a significant increase in TSA-treated groups compared to PFS+Saline. Conclusion: TSA with anti-inflammatory effects led to the reduction of hippocampal inflammatory cytokines and amelioration of spatial memory in offsprings who were exposed to stress in the prenatal period. Manuscript profile