Nickel nanoparticles (NiNPs) are used in catalysts for hydrogenation of dietary fats, in cosmetics, insecticides, preparations for theranostics in medicine, and can also expose people occupationally in the metallurgy and mining industry. Adverse effects of the long-term oral exposition to low doses of NiNPs are not well understood. The study aimed to evaluate the toxic effects of NiNPs at their 92-day administration to male Wistar rats as part of their diet at doses of 0.1; 1 and 10 mg/kg body weight. Two preparations of NiNPs were used, which contained spherical metal Ni particles with average diameters of 54 and 71 nm. As a result of oral exposure of animals to NiNPs, an increase in glycemia, triglyceride, LDL, total protein, and its globulin fraction levels was noticed. The intake of NiNPs by the animals caused a decrease in the reserves of reduced liver glutathione and excretion of selenium in the urine, an increase in serum levels of cytokines IL-1b, IL-2, IL-6, IL-12p70, TNF-a, and INF-g with a simultaneous decrease in IL-4 and IL-17A. In the liver of rats exposed to NiNPs, the expression of fibrosis-marking genes, such as MMp2, MMp9, and Timp3, increased. Light-optical microscopy revealed in these animals signs of liver inflammation, leukocyte and eosinophilic infiltration, lamina propria tint, and villus involution in the small intestinal mucosa. The severity of the toxic effects of NiNPs depended on their size and, in some cases, were more pronounced at their low or medium doses than at the highest one. Most of the manifestations of the toxic effect of NiNPs were absent in animals that were subjected to a soluble Ni salt in a metal-equivalent dose. The estimate of LOAEL for NiNPs was less than 0.1 mg/kg of body weight according to the indicators studied. Higher oral toxicity of NiNPs, when compared to the salt form of Ni, is presumably associated with their easier penetration through biological barriers, which requires additional studies.