Objective: Based on the NLRP3/Caspase-1/GSDMD pyroptosis pathway, a mouse model of LPS-induced acute lung injury was established over time, and the lung injury of mice was observed at different time points. According to the changes in injury at different time points and the expression of pyroptosis pathway-related proteins, the best time point for modeling was screened comprehensively, which laid the foundation for animal models for subsequent experiments. Methods: 54 six to eight weeks of SPF male BAL b/c mice were divided into nine groups randomly, which including control group and building time group (1, 3, 6, 12, 18, 24, 48 and 72 h group), body weight, lung tissue was detected in general and pathological observation and semi-quantitative score, lung index, lung water content of wet and dry weight ratio; The white blood cell count and the concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), IL-18 and BCA protein in bronchoalveolar lavage fluid (BALF) were detected. Using western blot method to detect the lung tissue of classic coke death pathways related NLRP3, pro - Caspase 1, Caspase 1, GSDMD protein expression. Results: According to the body weight statistics, the body weight of each group decreased, and the 24h and 48h groups showed the most significant weight loss. The results of gross observation and pathological examination of lung tissue showed that the injury of lung tissue in 24h to 72h was severe, and the difference between each group and Con group was statistically significant. Lung index, lung water content and wet/dry weight ratio were significantly increased at 24-72 hours. Alveolar lavage fluid white blood cells from 6 h after building began to rise, 48 h can reach a peak, 72 h all keep increasing; IL-18 in lavage fluid began to increase at 24 hours and continued to increase at 72 hours. TNF alpha, beta, IL - 6, IL - 1 inflammatory factors were keep the highest level at the time of 6 h, 48 h significantly reduced; A lavage in protein concentrations within 24 h, 48 h and 72 h compared with Con group were significantly increased; Found by western blot method and ALI model each time series jiao wu pathway proteins NLRP3, pro - Caspase 1, Caspase 1 and GSDMD protein expression were raised, 24 h - 72 - h group of channel protein expression enhanced significantly compared with control subjects. Conclusions: Comprehensive analysis of the experimental indicators, inflammatory factors and the expression of pathway proteins in WB in different time groups showed that the mechanism of pyroptosis was closely related to the occurrence and progression of ALI, and it moved with time. From the experimental results, it was found that the expression of pyroptosis pathway was the most obvious and the lung injury was the most serious in 24h-48h. This study provides a model reference and experimental basis for the subsequent study of the specific mechanism and intervention targets of ALI.