Background and Aim: Klebsiella pneumoniae is one of the most common causes of community-acquired and nosocomial infections and has acquired numerous resistance mechanisms over time. The aim of this study was to evaluate the antibiotic resistance pattern of clinical isolates of K. pneumoniae and investigate the mutations in Ompk35 porin as one of the most important mechanisms of resistance to beta-lactam antibiotics. Materials and Methods: In this cross-sectional correlation study, 100 urinary isolates of K. pneumoniae from the patients admitted to Milad Hospital were evaluated. Antibiotic susceptibility testing was performed using disk diffusion method. Using PCR method, ompK35 genes were detected, sequenced and the mutations were identified by use of Mega software (version 3. 7. 3). SPSS software version 20 and Chi-square test were used for data analysis. Results: The highest resistance rate belonged to amikacin (74%) followed by levofloxacin (69%). Resistance rates to cefepime, gentamicin, ciprofloxacin, meropenem, and ceftriaxone were 62, 58, 53, 41, and 35%, respectively. The highest sensitivity rate belonged to imipenem (80%). Numerous mutations were observed in the Ompk35 porin encoding genes. Among the isolates, 70% harbored mutations in Ompk35 protein and two isolates had five mutations simultaneously. There was no significant relationship between resistance to the antibiotics and gender in our study (P>0. 05). Conclusion: Our findings indicated a high prevalence rate of antibiotic resistance and high frequency of porin mutations among K. pneumoniae isolates. Also, the presence of similar mutations in the isolates suggests that they may have a common origin.