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Background: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP) is a risk factor for the peripheral arterial disease (PAD) in diabetes. This study aimed to evaluate the possible predictive significance of hs- CRP for the development and progression of PAD in patients with type 2 diabetes (T2D). Mathods: The study included 80 patients previously diagnosed with T2D, aged 45-70 years, divided into group A (T2D patients with PAD; n=38) and group B (T2D patients without PAD; n=42). After five years, all the patients were re-examined and divided into subgroups depending on de novo development of PAD or progression of previously diagnosed PAD. Ankle-Brachial Index (ABI) measurement was used for PAD diagnosis and hs-CRP was determined by nephelometry. Results: We found significantly higher hs-CRP levels in group A compared to group B, but only at baseline. Among the patients in group A, those with later progression of PAD (subgroup A1) had the highest levels of hs-CRP at baseline, although not significantly different from those in subgroup A2 (non-progressors). In contrast, hs-CRP level was significantly higher in subgroup B1 (progressors) in comparison to subgroup B2 (non-progressors) at both the first and sec-ond exam. Of all the investigated metabolic parameters, hs-CRP was the only independent predictor of PAD progression (OR=0.456, 95% CI=0.267-0.7815, p=0.004). The cut-off point for hs-CRP was 2.5 mg/L (specificity 75% and sensitivity 73.3%) with the relative risk for PAD of 2.93 (95% CI=1.351-6.3629). Conclusions: Our study implies that hs-CRP can be used as a reliable predictor for the progression of PAD in patients with T2D.