Introduction: This study highlights the subacute kidney toxicity of Wistar albino rats exposed to Caladium hortulanum leaf extract. Methods: Twenty-four (24) rats were randomly divided into 4 groups labelled A, B, C and D and kept in a well-ventilated room. Group A served as control and these rats were treated with distilled water. Rats in the groups B, C, and D were treated with 3 different doses of the sample (1.5, 3.5 and 5.0mL/KgBW) respectively. Samples were administered once daily for 14 and 28days consecutively. Animals were sacrificed 24 hours after the last treatment. Blood samples were collected into heparinized sample bottles for analysis. Results: Serum urea and creatinine concentrations increased in a dose dependent manner at all durations of administration. The increase became significant at 5.0ml/KgBW for 14 days of administration. This trend was present at all doses for 28 days of administration. Histology done showed normal kidney tissue architecture for short term use and at the lowest dose of 1.5ml/KgBW for long term use. Both 3.5ml/KgBW and 5.0ml/KgBW doses in the long term group showed abnormalities of destroyed renal tubules, absent glomeruli and occluded bowmans capsular spaces. Conclusion: This study demonstrates that prolonged use of this leaf extract increases the risk of kidney malfunctioning.