Objective To investigate the effects of minocycline (Mino) on the mechanical withdrawal threshold (MWT) and cold allodynia threshold, the proportion of p-p38 mitogen-activated protein kinase (p-p38 MAPK)-positive nuclei among pseudounipolar neurons in dorsal root ganglia (DRG), and the expression of inflammatory cytokines in a rat model of the spinal nerve ligation (SNL) model rats. Methods 27 adult male Sprague-Dawley (SD) rats were randomly assigned to three groups (n=9 per group) based on body weight using a stratified random sampling method: the sham-operated (Sham), the SNL group, and the Mino+SNL group (receiving intrathecal injection of minocycline). MWT and cold allodynia threshold of the ipsilateral hind paw were measured one day before surgery and on postoperative days 4, 7, 10, and 14. On postoperative day 14, the ipsilateral L5 DRG was harvested. The expression levels of TNF-α, IL-6, and IL-10 in the DRG were measured by ELISA. The proportion of p-p38 MAPK-positive neuronal nuclei among pseudounipolar neurons within the largest cross-sectional area of the DRG was assessed using immunohistochemistry. Results Compared with the Sham group, both the SNL and Mino+SNL groups showed a significant decrease in MWT and cold allodynia threshold on the ipsilateral side from postoperative days 4 to 14 (P<0.05). Compared with the SNL group, the Mino+SNL group exhibited a significant increase in MWT and cold allodynia threshold on the ipsilateral side from postoperative days 7 to 14 (P<0.05). On postoperative day 14, compared with the Sham group, the SNL group showed significantly increased protein expression of TNF-α, IL-6, and IL-10 in the ipsilateral DRG, as well as a significantly increased proportion of p-p38 MAPK-positive neuronal nuclei within the DRG cross-section (P<0.05). Compared with the SNL group, the Mino+SNL group demonstrated a significant increase in IL-10 expression (P<0.05), and significant decreases in TNF-α and IL-6 expression, as well as in the proportion of p-p38 MAPK-positive neuronal nuclei within the DRG cross-section (P<0.05).Conclusion Minocycline alleviates SNL-induced neuropathic pain, likely by inhibiting the inflammatory response in DRG, which subsequently suppresses p38 MAPK pathway activation and the nuclear translocation of p-p38 MAPK. Our study provides key morphometric support for the significant role of the p38 MAPK pathway in LDH-associated neuropathic pain