It has been suggested that dietary intake of lipids and fatty acids may influence cognitive function, however, the effect of lard intake during pregnancy and postpartum periods on cognitive function of mother remains to be elucidated. We investigated the effect and mechanism of consuming soybean oil (SO), the mixed oil of lard and soybean oil at the ratio of 1:1 (LS) and lard oil (LO) during the pregnancy and postpartum periods on cognitive function of the maternal mice. All pregnant C57BL/6JNifdc mice were fed with soybean oil diet during day 0-10 (the day when vaginal plugs appeared in female mice was recorded as day 0), and then randomly assigned to SO, LS and LO groups (n = 10) from day 11 to day 44. The time in center zone and the number of times to enter in center zone were significantly higher in the SO group than in the LO group detected by the open-field test. The levels of neuroglial cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex and pyroptosis related proteins in brain of the LO group were significantly higher than those in the SO group. RNA-sequencing results showed that the calcium signaling pathway related genes in brain, including , , , , and levels significantly higher in the LO group than in the SO group. Lipidomic analysis indicated that PG 18:2_18:2, PG 20:5_22:6, and CL 12:0_16:0_22:3_22:5 of glycerophospholipid metabolism in brain significantly connected with of calcium signaling pathway. In conclusion, the intake of lard during the pregnancy and postpartum periods is detrimental to the cognitive function of maternal mice, which probably due to changes in the composition of fatty acid in the brain, thereby activating neuroinflammation via calcium signaling pathway in brain.