Objective:To investigate the expression of endocan and FLK-1 in NSCLC, and to explore the correlation with angiogenesis and other clinical pathophysiological characteristics of NSCLC. Methods:The expression of endocan was detected by using immunofluorescence technique in 60 specimens of NSCLC and 21 specimens of adjacent non-cancerous tissues as control group. Immunohistochemical S-P method was performed to estimate the expression of FLK-1 and MVD. Results:The endocan-positive rate was 78.33%(47/60) in NSCLC group and 14.29%(3/21) in control group. The positive rate of FLK-1 was 71.67%(43/60)in NSCLC group and 19.05%(4/21) in control group. There was a significant difference between them(χ2 = 27.01,17.68; all P < 0.05). In stage Ⅰ+Ⅱ and Ⅲ+Ⅳ of NSCLC, the positive rates of endocan were 67.64%(23/34) and 92.30%(24/26) while the positive rates of FLK-1 were 58.82%(20/34) and 88.46%(23/26). The differences of endocan and FLK-1 expression between stageⅠ+Ⅱ and Ⅲ+Ⅳ were significant respectively(χ2=5.28, 6.37, all P < 0.05). In the group with lymph node metastasis and the group without lymph node metastasis, the positive rates of endocan were 84.78%(39/46) and 57.14%(8/14), the positive rates of FLK-1 were 80.43%(37/46) and 42.86%(6/14). The differences of endocan and FLK-1 expression between the two groups were also significant respectively(χ2 = 4.83,7.46,all P < 0.05). The MVDs in the endocan-positive group and the endocan-negative group were 25.16 ± 5.12 and 18.97 ± 3.28 respectively, the difference was significant(t = 4.52, P < 0.05). The MVDs in the FLK-1-positive group and the FLK-1-negative group were 24.65 ± 4.34 and 18.92 ± 3.35 respectively, the difference was also significant(t = 5.23,P < 0.05). There was positive correlation between the expressions of endocan and FLK-1 in NSCLC(r = 0.8889, P < 0.05). However, The positive rates of endocan were 77.42%(24/31) in adenocarcinoma, 80.00%(20/25) in squamous cell carcinoma and 75.00%(3/4) in large cell lung cancer. The positive rates of FLK-1 were 70.96%(22/31) in adenocarcinoma,72.00%(18/25) in squamous cell carcinoma and 75.00%(3/4) in large cell lung cancer. There was no significant difference among them(χ2=3.63,1.79, all P > 0.05). Conclusion:Endocan and FLK-1 might play very important roles in tumor angiogenesis in NSCLC.