Psoriasis is a chronic autoinflammatory disorder characterized by patches of abnormal skin. For psoriasis management, the application of topical retinoids as Tazarotene is recommended. However, Tazarotene could induce skin irritation limiting its use. Herein, it is evaluated the possible usage of in situ gels for tazarotene skin delivery. The topical in situ gels were developed using thermosensitive poloxamers via cold method. They were examined for their appearance, sol-gel temperature, clarity, pH, viscosity, in vitro release, and stability. Their biocompatibility was evaluated by investigating their cytotoxicity and irritation inducing capacity. The possible anti-inflammatory and analgesic activities were determined by measuring the nitric oxide and prostaglandin E-2 levels production in LPS-stimulated RAW264.7 murine macrophage cells. It was revealed that the in situ gels had no cytotoxic effect (similar to 95-100% cell viability) and nor irritation potential (similar to 97% cell viability), according to the in vitro EpiDerm (TM) reconstituted skin irritation test. Additionally, the 10% tazarotene-in situ gels showed possible analgesic activity since the production of prostaglandin E-2 (PGE(2)) was decreased. In further, both concentrations of 5% and 10% tazarotene-in situ gels inhibited significantly the nitrite oxide production at 16% and 19%, respectively. Finally, the prepared in situ gels can act as a potential non-irritant alternative option for tazarotene topical skin delivery.