Piperin in white pepper (Piper nigrum L) has a hepatoprotective effect, anti-inflammatory, anti-arthritis, antihypertensive and anti-asthma. This study aims to determine the toxic effects of subchronic piperine on liver damage scores and scores on the number of polymorphonuclear (PMN) cells in the liver and kidneys The method used is post only control group design. White pepper seeds were extracted by sochletation using ethyl acetate. The test subjects were 30 male mice, 2-3 months, 35-45 grams, divided into 5 groups namely piperine control, dose 17.5 mg / kg body weight, dosage 35 mg / kg body weight, dose 70 mg / kg body weight and dose 140 mg / kg body weight . Piperine administration is carried out orally for 21 days. All subjects were sacrificed on the 22nd day. Liver and kidney were taken and fixed with 10% formalin solution and preparations were made by painting HE. Preparations were given a liver damage score and a score of the number of liver and kidney PMN. Data were analyzed using the Kruskall-Wallis test and continued with the Mann-Whitney test. Score of liver damage in control group; dose of 17.5 mg / kgBB; dose of 35 mg / kgBB; the dose of 70 mg / kgBB and the dose of 140 mg / kgBB are: 1.13 ± 0.05; 1.53 ± 0.34; 1.91 ± 0.20; 2.10 ± 0.20 and 2.41 ± 0.14. Score of the number of liver PMN in the control group; dose of 17.5 mg / kgBB; dose of 35 mg / kgBB; the dose of 70 mg / kgBB and the dose of 140 mg / kgBB are 0.10 ± 0.08 respectively; 0.33 ± 0.10; 0.50 ± 0.08; 0.70 ± 0.11 and 0.88 ± 0.13. Score of the number of kidney PMN in the control group; dose of 17.5 mg / kgBB; dose of 35 mg / kgBB; the dose of 70 mg / kgBB and the dose of 140 mg / kgBB are: 0.03 ± 0.05; 0.21 ± 0.09; 0.50 ± 0.11; 1.01 ± 0.11 and 1.11 ± 0.13. The results of statistical tests on all parameters showed a significant difference between the control and the piperine group. Piperin in a subchronic for 21 days causes toxic effects characterized by changes in liver histopathology and increase in the number of PMN cells of the liver and kidneys. Damage increases with increasing dosage