Aim: Diabetes rising prevalence is of great concern in Africa because of its socioeconomic impacts in a context of limited access to health care. The inappropriate use of pesticides may add to the burden of diabetes in Africa. This study was carried out in a cotton producing area of Benin in order to assess the relationship between the highest prevalence of diabetes observed in the country and organochlorine pesticide (OCP) exposure. Methods: This was a case-control study conducted in 2011. A sample of 106 subjects with diabetes and 106 non-diabetic controls were paired by age, gender, ethnicity, and residential area. Personal and socioeconomic information, along with anthropometric measurements were collected. Blood samples were assayed for total lipids and 14 OCPs by gas-chromatography coupled with massspectrometry. Data were recorded for the four detectable OCPs: p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), β-hexachlorocyclohexane (β-HCH), and trans-nonachlor. Results: Serum levels of all four detected OCPs were consistently higher in diabetic subjects as compared to non-diabetic controls. The odds ratio (OR) of diabetes was nearly threefold higher when comparing the third tertile of p,p'-DDE and p,p'-DDT and β-HCH levels with the first tertile, without adjustment for potential confounders. The association remained significant for p,p'-DDT (OR = 2.59; 95% confidence interval (CI): 1.17-5.42) and p,p'-DDE (OR = 2.11; 95% CI: 1.01-4.54) after adjusting for a family history of diabetes, abdominal obesity, and wealth index or education. Conclusion: Our data showed that exposure to p,p'-DDT and p,p'-DDE was associated with an increased risk of diabetes. These findings have major public health implications.