Backgrounds Appendicitis is the most common and important emergency condition, in which most of the patients undergo appendectomy. The diagnosis of appendicitis is critical and the values of diagnostic laboratory tests are always discussed. The current study aimed at determining the diagnostic value of C-Reactive Protein (CRP) increase in the diagnosis of acute appendicitis.Methods & Materials The current cross sectional study examined 105 individuals referred to the emergency department of Shahid Motahari Hospital, Marvdasht, Iran, in 1012. Before the administration of any preoperational antibiotics, blood samples were obtained from the subjects to measure the serum CRP level. After surgery, the relationship among serum levels of CRP and appendix tissue biopsy, and the surgeon`s comments about the type of tissue were investigated. All data were analyzed by SPSS version 18, employing ANOVA and Tukey test. Results A total of 81 patients had acute appendicitis, out of which 24 had normal appendix. Among patients with acute appendicitis, 65 subjects showed increased serum CRP level and 16 subjects had normal serum CRP level. The sensitivity and specificity of CRP level in the study were 80% and 63%, respectively. Conclusion The results showed that evaluation of serum CRP levels can be useful and beneficial to diagnose acute appendicitis.