ObjectiveThis study investigated the vascularization in periodontal disease process via revealing: (i) vascular endothelial cadherin (VE‐cadherin) and vascular endothelial growth factor (VEGF) productions in periodontitis and (ii) the impact of smoking on this phenomenon.Materials and MethodsFifteen smokers and 15 non‐smokers with/without periodontitis were allocated by split‐mouth randomization regarding their smoking and periodontal statuses. The teeth with periodontitis in smokers (group 1), without periodontitis in smokers (group 2), with periodontitis in non‐smokers (group 3), and without periodontitis in non‐smokers (group 4) constituted the study groups. Gingival crevicular fluid (GCF) levels of VE‐cadherin and VEGF were determined by ELISA to evaluate their profiles in the groups.ResultsThere were increased VE‐cadherin levels in groups 1 and 3 compared with groups 2 and 4 (P < 0.05). Group 2 demonstrated higher VE‐cadherin level than group 4 (P < 0.05). Increased VEGF was noted in groups 1 and 3 compared with groups 2 and 4 (P < 0.05) with similar levels between groups 1 and 3 and groups 2 and 4 (P > 0.05). There were no correlations between the VE‐cadherin and VEGF levels in all groups (P > 0.05).ConclusionThe results suggest that VE‐cadherin and VEGF may increase in periodontitis, and smoking may uniquely cause VE‐cadherin production in GCF.