Objective: To evaluate the efficacy of several β-lactams against ESBL producing Klebsiella pneumoniae pneumonia in a mouse model of peneumonia. Methods: Two clinical Klebsiella pneumoniae strains susceptible to the experimental antimicrobial agents, Klebsiella pneumoniae GX6998 and Tian 29, were divided into two groups for mouse pneumonia infection respectively. After six-hour infection, mice were intraperitoneally injected with 0.5ml 0.9% NaCl for control; mice were intraperitoneally injected with ceftazidime, cefepime, cefoprazone plus sulbactam and piperacillin plus tazobactam respectively for trial. Seventy-two hours later, therapy efficacies were evaluated with bacterial counts. Results: All the trial groups had significantly lower mortality than control groups (P < 0.05). Compared with the control groups, in GX6998 infected groups, the bacterial amounts with all the testing agents were significantly decreased (P < 0.01); in Tian 29-infccted group, the bacterial amounts with cefoprazone plus sulbactam and ceftazidime were significantly decreased (P < 0.05); in cefepime and piperacillin plus tazobactam groups, bacterial amounts were reduced without significant difference with that of the control group (P > 0.05). Conclusion: The combinations of broad-spectrum β-lactams and β-lactamases inhibitor could reduce the mortality and bacterial amounts in mouse pneumonia model which were susceptible to ESBLs-producing Klebsiella pneumonia strains. However, the clinical efficacy would be reduced when the MIC increased.