Abstract: Background　Prenatal stress may influence offspring cognitive development through altered astrocytic lipid metabolism. Objective To investigate whether prenatal stress induces astrocytic lipid metabolism abnormalities, subsequently leading to cognitive dysfunction in offspring.Methods　Fourteen SD pregnant rats were randomly divided into a stress group (n=7) and a control group (n=7). The stress group underwent restricted stress from gestational days 15 to 21, while the control group was housed under conventional conditions. Adult offspring cognitive function was assessed using the open field test, elevated plus maze, novel object recognition test, and Y-maze test. Lipid droplet accumulation in the hippocampal astrocytes and lipid metabolism changes were detected in offspring using Oil Red O staining, qRT-PCR, Western Blot, and immunofluorescence staining. mRNA expression levels of inflammatory factors in hippocampal tissue and protein concentrations of inflammatory factors in peripheral blood were measured using qRT-PCR and ELISA, respectively.Results　Offspring in the stress group exhibited lower birth weight (P0) than the control group (P＜0.001). Body weight at all time points from birth to day 5 (P0-P5) was lower in the stress group than in the control group. The open field test revealed reduced total locomotor distance and central zone locomotor distance within 5 minutes in the stress group compared to the control group (P＜0.05). The elevated plus maze test revealed that compared to the control group, the stress group exhibited reduced entries into the open arms and decreased dwell time in the open arms (P＜0.001); The novel object recognition test showed no statistically significant difference in total object exploration time between the two groups, but the stress group exhibited a reduced novel object recognition index (P＜0.001). The Y-maze test revealed that compared to the control group, the stress group had reduced exploration time and movement distance in the novel arm (P＜0.05). Oil Red O staining revealed abundant red lipid droplets in the hippocampal region of the stress group. Western blot, qRT-PCR, and immunofluorescence staining results all indicated elevated expression of perilipin 2 (PLIN2) in the stress group (P＜0.01). Concurrently, qRT-PCR results demonstrated elevated relative mRNA expression levels of inflammatory cytokines IL-6, IL-1β, and TNF- α (P＜0.05). Further ELISA analysis revealed corresponding increases in the protein expression levels of these three inflammatory cytokines in the offspring's peripheral blood (P＜0.001). Conclusion　Prenatal stress may mediate cognitive dysfunction in offspring by inducing lipid droplet accumulation in hippocampal astrocytes and associated neuroinflammation.