Topical use of antibiotics is currently a widely accepted effective and safe treatment for topical infections. One potential strategy for improving topical administration of drugs is to encapsulate the drug in a colloidal carrier. Nonionic surfactant vesicles (niosomes) are promising drug carriers since they have potential applications in the delivery of hydrophobic or amphiphilic drugs. In this study niosomes encapsulated tetracycline hydrochloride (TC-HCl) were prepared by using lipid film hydration technique The effect of processing variables such as surfactant structure, drug concentration, lipid concentration and Charge inducing agents e.g. steary1 amine (SA) and dicety1 phosphate (DCP) on the percentage drug entrapped (PDE ) and in-vitro release of TC-HCI has been determined. The results showed that niosomes prepared from span 60 and 40 gave the highest PDE, (34.6, 30.29% respectively) followed by span 20 and span 80 (15.6, 14.6% respectively) using 300 µmole total lipid. Increasing the total lipid concentration from 150-500 µmole for span 60 resulted in an increase in PDE from 33-38.7%. Changing drug concentration from 25 to 100 mg produced non significant effect on PDE. Moreover, concerning the charge inducing agent, incorporation of DCP and SA showed an increase in PDE to 67.14 and 46% respectively. Niosomes mean size showed a dependence on the HLB of span used, The lower the HLB the smaller the niosomal mean size In-vitro release studies indicated that niosomal vesicles could retain a considerable amount of TC-HCI over prolonged period of time (24 hrs) for span 60 chol (1:1)  niosomes. The in-vitro antimicrobial activities of niosomes-encapsulated TC-HCI in comparison with that of free TC-HCH against clinical isolates isolated from skin infection showed that, TC-HCI encapsulated in either cationic or anionic niosomes  was more active than TC-HCI encapsulated in neutral niosomes. The minimum inhibitory concentrations (MICS) for niosomes-encapsulated TC-HCI were significantly lower than those of the corresponding free TC-HCI. Niosomes-encapsulated TC-HCl showed greater antimicrobial activities than the free form. In conclusion, these drug formulations may have potential in the treatment of topical bacterial infections.