Objective Use aspirin to induce mouse inflammatory bowel disease model, and investigate whether Lactobacillus acidophilus LA-GHB1756 can alleviate this type of enteritis injury. Methods A total of 40 male BALB/c mice (6-8 weeks old) was randomized into four groups: control group, aspirin group, LA low-dose group, and LA high-dose group. Except for the control group, the remaining groups were given 0.5 mg/(100 g·d) aspirin solution by gavage for eight weeks to induce inflammatory bowel disease. The LA low-dose and high-dose groups received an additional 2000 cfu/(100 g·d) and 10 000 cfu/(100 g·d) of LA-GHB1756 bacterial liquid, respectively. Accordingly, the control and aspirin groups received the same volume of normal saline through gavage. We then monitored the mouse's body weight, defecation status, hair color, and other conventional indicators, colon macroscopic and pathological staining. We used ELISA to detect intestinal tissue MPO content, serum tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) expression. We employed Western blotting to detect intestinal tissue NF-κB p65 expression levels. Results The general observation of mice in each group showed that LA-GHB1756 could improve the diarrhea, hair, and mental status of aspirin-induced mice. In the 8th week, the body weight of mice in the aspirin group was (21.6±0.5) g. The body weight was statistically significantly improved in the LA low-dose and high-dose groups, which were (22.8±0.4) g and (23.1±0.3) g, respectively (P<0.05). The colon morphology and pathological results showed that LA-GHB1756 could alleviate intestinal mucosal edema and inflammation caused by aspirin in mice. The colon length of mice in the aspirin group was(5.80±0.43) cm, and the colon length of low-dose and high-dose LA groups was (6.17±0.15) cm and (6.50±0.26) cm, respectively. This length improvement was statistically significant (P<0.05). The results of MPO content in intestinal tissues showed that aspirin group was (95.90±11.34) pg/mg, the MPO content in LA low-dose group and LA high-dose group were (76.03±8.72) pg/mg and (51.40±9.12) pg/mg respectively, which was significantly decreased compared with aspirin group, the difference was statistically significant (P<0.05). The results of serum TNF-α and IL-6 expression showed that the concentrations of TNF-α and IL-6 in aspirin group were (238.75±17.80) pg/mg and (292.00±15.51) pg/mg, respectively, while those in LA low-dose group were (207.75±12.04) pg/mg and (250.25±11.50) pg/mg, respectively, LA high-dose group were (80.25±10.24) pg/mg and (108.50±13.38) pg/mg, respectively. Compared with aspirin group, TNF-α and IL-6 contents in LA low-dose group and LA high-dose group were statistically significantly decreased (P<0.05). The expression of NF-κB p65 was increased up to 5.07 fold in aspirin group when compared with control group. This level was statistically significantly decreased to 83.74% and 82.95% in LA low-dose and high-dose groups, respectively (P<0.05). Conclusion LA-GHB1756 can relieve intestinal inflammation in mice caused by aspirin, this effect may be related to the inhibition of MPO and NF-κB p65 expression in intestinal tissue.