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Background: The effects of collagen-induced arthritis (CIA), a model of systemic inflammation, on brain regional molecular markers associated with neurological disorders are uncertain. Objective: This study investigated the brain regional molecular changes in markers associated with inflammation and neuronal dysfunction in a CIA model. Methods: Fourteen male Sprague Dawley rats were divided into control (n = 5) or CIA (n = 9) groups. 10 weeks after CIA induction, brain tissue was collected. Brain regional mRNA expression of inflammatory markers (<i>IL-1β</i> and <i>IL-6</i>), apoptotic markers (<i>BAX</i> and <i>Bcl2</i>) and neurotrophic factors (<i>BDNF</i>, <i>CREB</i> and <i>TrkB</i>) was determined. Monoamine distribution and abundance in different brain regions were determine by mass spectrometry imaging (MSI). Results: Neuroinflammation was confirmed in the CIA group by increased <i>IL-β</i> mRNA expression, concurrent with an increased <i>BAX/Bcl2</i> ratio. The mRNA expression of <i>CREB</i> was increased in the midbrain and hippocampus while <i>BDNF</i> was increased and <i>TrkB</i> was decreased across all brain regions in CIA compared to control animals. Serotonin was decreased in the midbrain and hippocampus while dopamine was decreased in the striatum of CIA rats, compared to controls. Conclusion: CIA resulted in neuroinflammation concurrent with an apoptotic state and aberrant expression of neurotrophic factors and monoamines in the brain, suggestive of neurodegeneration.