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The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (<i>TLR4</i>), proinflammatory cytokines (<i>IL1B</i>, <i>IL6</i>), their receptors (<i>IL1R1</i>, <i>IL1R2</i>, <i>ILRN</i>, <i>IL6R</i>, <i>IL6ST</i>) and inflammasome components necessary for pro-IL-1β activation (<i>NLRP3</i>, <i>PYCARD</i>, <i>CASP1</i>), chemokine (<i>CCL2</i>), leptin receptor isoforms (<i>LEPRa</i>, <i>LEPRb</i>) and a suppressor of cytokine signalling (<i>SOCS3</i>) in the ChP of ewes treated or not with lipopolysaccharide (LPS). Studies were conducted on adult female sheep divided into four groups (<i>n</i> = 6 in each): control, leptin (20 μg/kg), LPS (400 ng/kg), and LPS and leptin injected under SD and LD photoperiods. The leptin alone did not affect the gene expression but in co-treatment with LPS increased (<i>p</i> < 0.05) IL1B but only during SD, and <i>SOCS3</i>, <i>IL1R2</i>, <i>IL1RN</i>, <i>IL6ST</i> and <i>CCL2</i> only during LD, and decreased (<i>p</i> < 0.05) the <i>IL1R1</i> expression only during SD photoperiod. This indicates that the immunomodulatory action of leptin on the ChP is manifested only under the LPS challenge and is photoperiodically dependent.