Objective To investigate the effect of embryonic inflammatory exposure on the offspring response to IRBP-induced experimental autoimmune uveitis (EAU). Methods RNA transcriptome sequencing data from eyeball in the C57BL/6J offspring gestated from active parental EAU were used to screen immune-associated differentially expressed genes (DEGs) in the eyes of exposed offspring. Gene fragments overlapping in the two datasets were screened using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses to identify biological pathways associated with gene fragments. Hub genes were identified from these intersecting genes by protein-protein interaction networks (PPI) analysis. EAU models of offspring affected by maternal uveitis were established by immunization with IRBP651-670, and the expression levels of the pivotal genes in the offspring exposed to inflammation by maternal uveitis were examined by fluorescence quantitative polymerase chain reaction (q-PCR). The EAU severity, T lymphocytes proliferation and serum cytokines were detected to investigate the immune effect of offspring gestated from materinal active inflammation response to 150 μg IRBP induction. Results Microarray analysis identified 72 immune-related genes in ocular tissue DEGs compared with control samples. These genes were mainly enriched in pathways involved in Toll-like receptor signaling pathway, MAPK signaling pathway, and B cell receptor signaling pathway. Further PPI network interaction analysis screen out four hub genes, namely, Psmc5, Psmc3, Psmd4, and Psmd8. Meanwhile the adult offspring gestation from materinal active uveitis expressed increased mRNA level in those four hub genes compared with those healthy offspring. In addition, under 150 μg IRBP induction, an increase in the severity of EAU in the offspring during the inflammatory activity period was observed, with significant differences in clinical and pathological aspects compared with the control group. Meanwhile, the proliferation of T cells in the offspring during the inflammatory activity stage was enhanced, and the secretion of inflammatory cytokines IL-17 and IL-6 was increased. Conclusions Psmc5, Psmc3, Psmd4, and Psmd8 may be the important genes exacerbating offspring uveitis associated with the increased T cell proliferation and production of IL-17 and IL-6.