Naftidrofuryl improves the blood supply and ischemic damage of the vessel wall by blocking specifically 5-hydroxytryptamine-2 (5-HT2) receptors without influencing the general circulatory bed and improves glucose aerobic metabolism by an action on succinodehydrogenase.The aim was to evaluate the effect of naftidrofuryl on vasomotor dysfunction in diabetic patients with peripheral arterial occlusive disease (PAOD) and coronary artery disease (CAD). The subjects were 10 type-2 diabetic patients with both PAOD and CAD who received a 600 mg daily dosage of naftidrofuryl orally for 12 weeks. 20 healthy subjects were selected as controls. The patient groups were matched for age, sex and body mass index. The diagnosis of CAD was substantiated by coronary angiography. All the patients had a decreased ankle-brachial index in both legs (0.73 ±0.17). We recorded changes in laser Doppler flux (LDF; PeriFlux 4001, Perimed) induced by a 3 min arterial occlusion on the pulp (apical skin) of the big toe. Basal LDF (b-LDF), postocclusive hyperaemia (m1-LDF), vasoconstrictor response (v-LDF) to deep inspiration (in apical skin), and heat (44 oC; PeriTemp 4005) induced hyperaemia (m2-LDF) on the dorsum (non-apical skin) of the big toe were estimated using a PeriSoft programme. After the therapy the following indices were improved (mean±SD): b-LDF at both locations (apical skin: 48±34 vs 78±42 PU, p<0.005; non-apical skin: 14±9 vs 27 ±24 PU, p<0.05), v-LDF (13.5±12.4 vs 26.7±15.5%, p<0.0001), m1-LDF (100±54 vs 133±60 PU, p<0.01) and m2-LDF (61±31 vs 95±49 PU, p<0.01). Our results suggest that 12 weeks of naftidrofuryl therapy improves the cutaneous vasomotor response in diabetic patients with CAD and PAOD.