Objective To investigate the mechanism of Luo's Bazi Fenjin Manipulation in treating rats with chronic compression of dorsal root ganglion. Methods Thirty SD rats were randomly divided into blank group, model group, sham operation group, manipulation group, or ammonium 1⁃pyrrolidinedithiocarbamate (PDTC) group, with 6 rats in each group. Rats in the model group, manipulation group, and PDTC group were used to establish a chronic compression of dorsal root ganglion model. Rats in the manipulation group were intervened with Luo's Bazi Fenjin manipulation, and rats in the PDTC group were intraperitoneally injected with PDTC for 12 consecutive days, whereas the blank group, model group, and sham operation group received no intervention. The paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PWTL) of rats in each group were measured 1 day before modeling and on the second and 14th day after modeling, respectively. On the 14th day after modeling, HE staining was used to observe the pathological changes of the spinal cord tissue of rats in each group, ELISA was adopted to detect the serum levels of interleukin 6 (IL⁃6) and tumor necrosis factor α (TNF⁃α) of rats in each group, PCR was employed to detect the mRNA expressions of C⁃X⁃C motif chemokine ligand 1 (CXCL1) and C⁃X⁃C motif chemokine receptor 2 (CXCR2) in dorsal horn tissue of the spinal cord of rats in each group, and Western blot was used to detect the protein expressions of phosphorylated nuclear factor κB p65 subunit (p⁃NF⁃κB⁃p65), phosphorylated nuclear factor κB inhibitor protein (p⁃IκB), CXCL1, and CXCR2 in dorsal horn tissue of the spinal cord of rats in each group. Results On the 14th day after modeling, compared with the model group, the degree of spinal cord pathological injury in the manipulation group was alleviated, the PMWT and PTWL were increased, the serum levels of TNF⁃α and IL⁃6 were decreased, and the protein expressions of p⁃IκB and p⁃NF⁃κB⁃p65, as well as the mRNA and protein expressions of CXCL1 and CXCR2 in dorsal horn tissue of the spinal cord were decreased (P<0.05). Conclusion Luo's Bazi Fenjin Manipulation can regulate the expressions of CXCL1 and CXCR2 through the nuclear factor κB signaling pathway, thereby alleviating hyperalgesia and inflammatory response induced by chronic compression of dorsal root ganglion, and exerting anti⁃inflammatory and analgesic effects.