〔Abstract〕 Objective To evaluate the effect of imipenem cilastatin sodium on pulmonary inflammatory response in the treatment of severe pneumonia. Methods A total of 83 patients with severe pneumonia admitted to Jiamusi Central Hospital from May 2019 to April 2020 were selected and divided into group A (41 cases, moxifloxacin) and group B (42 cases, Imipenem and cilastatin sodium) using a random number table method, to compare the clinical efficacy, inflammatory factor levels, and adverse reactions between the two groups. Results The total effective rate of clinical treatment in group B was significantly higher than that in group A, and the difference was statistically significant (P < 0.05); After treatment, procalcitonin (PCT) and high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) inflammatory factor levels in group B were lower than those in group A, the differences were statistically significant (P < 0.05); The incidence of adverse reactions in group B was lower than that of group A, and the difference was statistically significant (P < 0.05). Conclusion The application of imipenem cilastatin sodium in the treatment of severe pneumonia has a significant clinical effect, a reduced level of inflammatory factors, and fewer adverse reactions.