Objective To explore the method of establishing the animal model of acute exacerbation of idiopathic pulmonary fibrosis in rat, and explore the usage and dosage of the inducer lipopolysaccharide. Methods 150 healthy male Wister rats were randomly divided into negative control group (Control group), remission control group (IPF group), acute exacerbation control group (BLM group), lipopolysaccharide low dose group (LPS-low group), lipopolysaccharide medium dose group (LPS-mid group), and lipopolysaccharide high dose group (LPS-high group). The Control group was induced by first intratracheal injection of 0. 9% sodium chloride injection combined with second intraperitoneal injection of 0. 9% sodium chloride injection(day 0, 0. 1 mL/100 g; day 28, 0. 5 mL/100 g). The IPF group was induced by the first intratracheal injection of bleomycin combined with the second intraperitoneal injection of 0. 9% sodium chloride injection (day 0, 5 mg/ mL, 0. 1 mL/100 g; day 28, 0. 5 mL/100 g). The BLM group was induced by two consecutive intratracheal injections of bleomycin (day 0, 5 mg/ mL, 0. 1 mL/100 g; day 28, 7 mg/ mL, 0. 1 mL/100 g). LPS-low group, LPS-mid group and LPS-high group were induced by the first intratracheal injection of bleomycin combined with the second intraperitoneal injection of lipopolysaccharide (day 0, bleomycin, 5 mg/ mL, 0. 1 mL/100 g; day 28, lipopolysaccharide, 2.5 mg/ mL, 5 mg/ mL, 7.5 mg/ mL, 0. 5 mL/100 g). Take samples on the 31st, 35th, and 42nd days after the first molding. Observe the survival status of rats, lung tissue wet to dry weight ratio (W/ D), lung coefficient, lung tissue HE staining, lung tissue Masson staining, lung CT, lung function, arterial blood gas analysis, bronchoalveolar lavage fluid (BALF) composition analysis (total cell count, neutrophil count, IL-6 mass concentration, TNF-α mass concentration), lung tissue hydroxyproline (HYP) content, and lung tissue α-SMA immunohistochemistry analysis. Results (1) The LPS-low group, LPS-mid group, and LPS-high group rats showed significant wheezing, dyspnea, cyanosis of the paw lips, decreased body mass, and increased mortality rate. (2) The W/ D value and lung coefficient of rats in LPS-low group, LPS-mid group and LPS-high group increased significantly, and acute pulmonary edema appeared. The performance of LPSmid group and BLM group was more consistent (P> 0. 05). (3) The histopathological changes in the LPS-low, LPS-mid, and LPS-high groups were consistent with the classic pathological manifestations of the disease. (4) The LPS-low group, LPS-mid group, and LPS-high group had patchy cotton wool like shadows on CT scans of the lungs, accompanied by irregular density enhancement shadows. (5) The lung function and blood gas analysis structure of the LPS-low group, LPSmid group, and LPS-high group showed a downward trend, with the LPS-mid group and BLM group showing more consistent performance (P> 0. 05). (6) The total cell count and neutrophil count in the alveolar lavage fluid of rats in the LPS-low, LPS-mid, and LPS-high groups increased, while the mass concentration of TNF-α in the alveolar lavage fluid and IL-6 in the serum increased. Among them, the LPS-mid and BLM groups performed more consistently (P> 0. 05). (7) The LPS-low group, LPS-mid group, and LPS-high group showed an increase in HYP content and α-SMA expression in the lung tissue of rats. Among them, the LPS-mid group and BLM group showed more consistent performance (P> 0. 05). Conclusions This method can successfully prepare a rat model of acute exacerbation of idiopathic pulmonary fibrosis. The optimal dosage of lipopolysaccharide is 5 mg/ mL, and the optimal observation time is the 31st day.