Our results showed that CUMS stimulation increased the expression of cGAS, STING, NLRP3, TBK1, and IRF3 in the CGAS-STING pathway in depressed mice, while EA and cGAS intervention reversed these changes, suggesting that the effect of EA on depression might be mediated by inhibiting the CGAS-STING pathway. This evidence concerns the gene NLRP3 and major depressive disorder.