Aims To study change in tear protein profile with duration of diabetes and severity of diabetic retinopathy (DR) in type 2 diabetes patients.Materials and methods Tear protein profile was ascertained by SDS PAGE method in 30 patients with DR (group A) and 37 patients without DR (group B).Results Six distinct bands of proteins were identified; these proteins are as follows: 91 kDa (P1), 66 kDa (P2), 60 kDa (P3), 30 kDa (P4), 18.4 kDa (P5) and 14.4 kDa (P6). Prevalence of P3 was significant (p = 0.036) in group A, especially in cases with diabetes ≥8 years compared with diabetes >8 years (p = 0.0107). In group B, P2 was significantly prevalent (p < 0.0013) in cases with diabetes ≥;8 years compared to diabetes >8 years. Considering the changes in terms of duration of diabetes in general, patients with diabetes of ≥8 years, P3 was significantly prevalent in group A compared to group B (p = 0.004); and when the duration of diabetes is >8 years, P2 was found significantly more in group A compared to group B (p = 0.01). No significant difference in P3 (p = 0.025), P4 (p = 0.2877), P5 (p = 0.4801), P6 (p = 0.0985) was observed in mild to moderate NPDR group compared to severe NPDR to PDR group. P1 and P2 were present only in severe NPDR and PDR.Conclusion Variable protein expression was observed with duration of diabetes and severity of diabetic retinopathy. © 2014 Diabetes India. © 2014 Diabetes India.