Objective To investigate the role of Chrm3 in regulating LPS-induced inflammation after LBP deletion in peritoneal macrophages of LBP knockout (Lbp-/-) mice. Methods Peritoneal macrophages of WT and Lbp-/- groups were isolated to establish an inflammation model induced by LPS. Chrm3 expression in Lbp-/- mouse peritoneal macrophages was inhibited by 4-damp and siRNA. Chrm3 expression was overexpressed by lentivirus. The inhibitor method were divided into a control group, LPS group, and inhibitior group. For siRNA transfection, cells were also divided into control group, LPS group, si-NC group, and si- Chrm3 group. And overexpress ion method were divided into control group, LPS group, negative control group and overexpression group. Changes in the Chrm3 response to LPS stimulation were verified by Western blot. Other methodologies, such as CCK-8, qPCR, and western blot assays, were used to confirm the effect in cell inflammation and the survival rate by 4-damp、si-Chrm3 and lentivirus. Results Significant elevation in Chrm3 protein expression in Lbp-/- peritoneal macrophages was observed post-LPS stimulation (P＜0.001). whereas no notable change was found in the wildtype. A remarkable increase in the cell survival rate was noted in 4-damp and si-Chrm3 groups (P＜0.05,P＜0.01) and the cell survival rate was reduced in overexpression group(P＜0.01). Furthermore, 4-damp and si-Chrm3 groups exhibited significantly reduced expression of inflammatory factors TNF-α、IL-1β and IL-6(P＜0.01,P＜0.001), and p-ERK(P＜0.01,P＜0.001), which are associated with cell damage and inflammation. In contrast,the expression of inflammatory factors TNF-α、IL-1β and IL-6(P＜0.001), and the phosphorylation of p-ERK protein(P＜0.001)were significantly elevated in the overexpression group. Conclusions Following LPS stimulation, upregulation of Chrm3 and proinflammatory cytokine expression was observed in Lbp-/- peritoneal macrophages. Specific downregulation of Chrm3 expression using 4-damp and si-Chrm3 significantly decreased LPS-induced proinflammatory cytokines in Lbp-/- peritoneal macrophages. The upregulation of Chrm3 using overexpressing lentivirus significantly elevated the levels of related inflammatory factors. Chrm3 is implicated in the regulation of the LPS-induced inflammation response in peritoneal macrophages of Lbp-/- mice.