Oral administration of chloroquine (CHQ) evokes adverse effects on glucose homeostasis and kidney function in African children probably due to high plasma CHQ concentrations or malaria parasites[1]. Studies indicate that oral administration of amidated-pectin chloroquine beads formulation sustains controlled release of CHQ into the bloodstream[2]. Accordingly, we speculated that CHQ administered via amidated CHQ-pectin patch sustains, controlled release of CHQ into the bloodstream. Hence, the current study investigated whether CHQ delivered via the transdermally can reduce malaria parasites and avert the reported adverse effects associated with oral CHQ route. The amidated pectin-CHQ patch was prepared using a protocol previously described with slight modifications [3]. Briefly, pectin was dissolved in deionized water followed by adding CHQ, DMSO and antioxidants. After freezing, CaCl2 was added for cross-linking. Parasitaemia, blood glucose and renal function were monitored in groups of non-infected and Plasmodium berghei-infected male Sprague-Dawley rats following twice daily oral (30 mg/kg) or a once-off transdermal delivery (53 mg/kg) of CHQ. These parameters, were monitored over a 21-day period divided into pre-treatment (days 0-7), treatment (days 8-12) and post-treatment (days 13-21). Transdermal delivery of CHQ and oral CHQ equally reduced P. berghei parasites to levels that were undetectable by day 5 of treatment. Oral administration of CHQ significantly decreased blood glucose concentrations of both the non-infected and infected animals. Interestingly, the once-off topical application of the pectin-CHQ patch increased blood glucose concentrations of P. berghei-infected animals. Furthermore, oral CHQ treatment was associated with increased urinary Na+ outputs and hyperkalaemia in both non-infected and P. berghei-infected rats. The CHQ matrix patch did not influence these parameters. Additionally, there was no statistical difference in plasma CHQ concentrations following treatment with either oral or transdermal CHQ. We conclude that transdermal CHQ delivery not only delivers CHQ into the systemic circulation, but also has the potential to ameliorate the pathophysiological effects associated with oral CHQ treatment.