This study aimed to observe the temporal changes in inflammatory factors and explore the mechanisms regulating inflammation during the shock period following debridement in rats. A burn model was established in SD rats using a 30% total body surface area III-degree scald. Rats were divided into three groups: control group, debridement group (12 hours post-burn debridement with heterograft skin coverage), and sham surgery group (simulated debridement with autograft skin coverage). Serum samples were collected at 12, 24, 48, 72, and 96 hours post-injury to assess levels of inflammatory factors and proteins related to the p38 MAPK/NF-κB pathway. The levels of lipopolysaccharide-binding protein (LBP), high-mobility group box 1 (HMGB1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-10 in the control group peaked between 12 and 48 hours post-injury, while HMGB1 increased gradually, peaking at 96 hours. Compared to the control group, both the debridement and sham surgery groups showed significant reductions in these inflammatory factors (P<
0.01 or P<
0.05), except for LBP. Liver p38MAPK levels showed no significant difference between groups, but phosphorylated p38MAPK and NF-κB levels significantly decreased (P<
0.05 or P<
0.01). In the debridement group, intra-group comparisons revealed a significant downward trend in inflammatory factors and liver p38MAPK and NF-κB phosphorylation levels. These results suggest that debridement during the shock period can reduce inflammation through the p38MAPK/NF-κB pathway, promoting a faster decline in systemic inflammatory response.