Bioavailability of a drug is critical factor affecting its efficacy. This parameter for every new brand or a new batch of the brand can be tested by in vivo bioequivalence studies on human volunteers where the equivalence in bioavailability of the tested brand is compared to that of an innovator reference one. These studies requires availability of huge budget, qualified personnel and specific technical requirements and hence, unfortunately, are difficult if not impossible to be carried out in poor countries such as Yemen. Therefore, the approaches of using alternative methods such as animal models, under ethical approval, may be suitable alternatives to the expensive in vivo methods. The present study was alongside those alternative approaches as it aimed to predict bioequivalence of ciprofloxacin HCl 500 mg tablet-brands marketed in Yemen using in vitro dissolution and animal intestinal permeability tests. Five test brands and one innovator brand of the drug were investigated in this study. In addition to drug content and in vitro dissolution, the rat intestinal permeability experiment using rat gut sac model, was carried out for each brand. The drug content and dissolution of all brands were within the pharmacopeial limit with exception of one test brand whose cumulative dissolved% was lower than pharmacopeial limit and also not similar to that of the innovator brand. On the other hand, the permeability ratios of only two test brands were within the range of 0.80-1.25. Since the drug has low solubility and permeability, the two brands which showed similar dissolution and permeability to the innovator brand could be predicted to be bioequivalent to it.