Background: Psoriasis is a T-cell mediated immunological disorder with numerous cytokines and adhesion molecules at play in its pathogenesis. Role of TNF-α, IL-1β and E-selectin has been studied by a few authors. But the studies are very limited in number. We plan to study these markers before and after topical therapy in patients of Psoriasis. Aims and Objectives: To study the serum levels of sE-selectin, TNF-α and IL-1β in patients of psoriasis and compare them with controls, Psoriasis Severity index and with each other. Material and Method: A prospective study of patients presenting with newly diagnosed Psoriasis at Dermatology OPD of Smt. Sucheta Kriplani Hospital, New Delhi. Follow-up was done after topical therapy with Coal tar, Salicylic acid and Dithranol. A total of 6 patients could be followed up. Serum samples were taken for ELISA determinations of TNF-α, IL-1β and sE-selectin at diagnosis and at 6 months follow-up visit. Results: In the present study the cases ranged from 8 to 50 years. Four patients had psoriasis vulgaris, 1 had Palmoplantar psoriasis and one had Pustular psoriasis. PASI Score ranged from 1.6 to 8.8. sE-selectin level in cases was 177.4±81.21ng/ml and reduced after therapy to 101.17±34.64ng/ml (p=.092). TNF-α level in cases was 32.05±42.27 pg/ml and reduced after therapy to 14.31±15.25pg/ml (p=.201). IL-1β levels in cases was 20.78 ±18.80 pg/ml and after therapy the levels reduced to 9.13±5.74 (p=.210). Conclusion: sE-selectin, TNF-α and IL-1β levels are increased in patients with psoriasis vulgaris as compared to controls. After therapy the levels reduce from the initial value but not enough to reach a statistical significance and remain higher than controls. This shows that these markers play an integral role in the pathogenesis and can be essential targets in formulation of newer therapies. Further studies as required to advance our knowledge in possible newer treatments for Psoriasis.