Objectives: To determine the prevalence and predisposing factors of mucormycosis in patients with diabetes mellitus (DM) in a Shiraz referral centers.Methods: This retrospective case control study, reviewed the medical records of 162 patients with pathologically confirmed diagnosis of mucormycosis hospitalized in two major Shiraz University hospitals during the last 21 years. For each diabetic patient, two patients with diabetic ketoacidosis (DKA) matched for age, sex and the date of admission was selected as control group. Age, type of diabetes mellitus (DM) and duration of involvement as well as paraclinical findings were compared between cases and controls.Results: There were 162 patients with murormycosis of which 30 (18.5%) had DM as predisposing factor. Diabetes was the second common predisposing disease next to leukemia. There were 19 (63.3%) women and11 (36.7%) men among the patients. The overall mortality rate was 53.33% mortality rate. The mean age of the patients was 45.3 ± 17.6 years. The mean duration of diabetes in case and control groups were 5.75 ± 5.43 and 7.2 ± 7.85 years respectively, without any statistical significance between them (p=0.063). Blood sugar in patients was lower than control group (p=0.012). Serum bicarbonate level in case group was higher than in control group (p<0.001). Arterial pH in control group was more acidic than case group (p<0.001). Insulin dependent DM was significantly more prevalent in control group compared to case group (73.4% vs. 36.6%; p=0.002).Conclusion: Our study showed that the number of hospitalized patients with mucormycosis over the last 7 years has been decreased which is due to better control of infection in diabetics. In addition to hyperglycemia and acidosis, several other unknown factors like immune defects may predispose diabetics to this fungal infection.