Aim of the work: The aim of the present work was to correlate between serum level of leptin, matrix metalloproteinase-13 (MMP13), interleukin-1b (IL1b), tumour necrosis factor (TNFa), nitric oxide (NO) and functional impact in obese patients with knee osteoarthritis (KOA).Patients and methods: The study included 84 obese patients suffering from primary KOA. The knees were examined; pain assessed by visual analogue scale (VAS) and Lequesne's index for functional impact calculated. Serum leptin, MMP13, IL1b, TNF-a and NO were assessed.Results: The mean age of the patients was 54.64 ± 7.7 years. They were 72 females and 12 males (F:M = 6:1) with a mean BMI of 35.29 ± 4.8. Sixty patients had knee effusion which was bilateral in 54 (64.3%), unilateral in 6 (7.2%) while 24 (28.6%) did not have any effusion. Knee deformities were present in 60 (71.4%) patients. Female patients were only significantly higher than males regarding Lequesne's index (15.08 ± 4.4 vs 11 ± 3.4, p = 0.003). Patients with knee deformity had significantly higher VAS (9.12 ± 1.3 vs 6.96 ± 0.46, p = 0.001), IL1b (621.1 ± 98.8 vs 503.9 ± 74.6 pg/ml, p = 0.001), TNF-a (115.4 ± 29.1 vs 87.4 ± 4.4 pg/ml, p = 0.001), NO (67.32 ± 5.7 vs 59.2 ± 2.2 lmol/L, p = 0.001), MMP13 (33.98 ± 2.24 vs 30.1 ± 1.7 ng/ml, p = 0.012) and leptin (13.2 ± 1.6 vs 10.4 ± 0.6, p = 0.004) than those without. The VAS, Lequesne index, IL1b, TNF-a NO, MMP13 and leptin were significantly higher in patients with bilateral knee effusion (p < 0.0001 for all) compared to those with unilateral effusion or without. Leptin significantly correlated with BMI, VAS, Lequesne's index, IL1b, TNFa, NO and MMP13 (p < 0.0001 for all).Conclusion: Leptin plays a key role in obese patients with knee OA. It significantly correlates with knee pain, functional impairment, inflammatory cytokines and cartilage degradation.