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Lactoferrin is a multifunctional glycoprotein of the transferrin family with a molecular mass of about 80 kDa. We studied the effect of human lactoferrin on stress- and lipopolysaccharide-induced changes in blood corticosterone levels, as well as on the gene expression of the cytokine IL4 and the pattern-recognition receptor TLR4 in rat splenocytes. Stress in rats was modeled by swimming in cold water (1-4°C) for 2 min. Lactoferrin and lipopolysaccharide (LPS) were administered intraperitoneally before the stress exposure. Corticosterone level in the plasma was determined by enzyme immunoassay, and changes in gene expression were assessed by real-time polymerase chain reaction (PCR) with reverse transcription. We showed that preventive intraperitoneal administration of lactoferrin reduced the stress and LPS-induced increase in the gene expression of both IL4 and TLR4 in rat splenocytes but did not change the concentration of corticosterone in the blood.