Alzheimer’s disease (AD) is the most frequent form of dementia in older people. Elevated levels of beta-amyloid(Aβ) peptide causes oxidative stress which lead to a gradual impairment of memory. Neurogranin(RC3) and neuromodulin (GAP43) play an important role in the learning and memory. Pioglitazone(Pio) and retinoic acid (RA) have antioxidant properties. In addition, pioglitazone improved cognitive performance in Alzheimer’s patients. Previously, we have demonstrated that an icv injection of Aβ(1-42) modified the daily rhythms of oxidative stress parameters and cognition-related factors in the hippocampus of rat. Continuing with that study, the objective of this work was to evaluate the effect of Pio/RA on RC3 and GAP43 expression as well as on Aβ protein levels, lipid peroxidation and protein carbonyls throughout a 24 h period, in the hippocampus Aβ-injected rat. Four-month-old male Holtzman rats divided into the groups control, Aβ-injected and Aβ-injected treated with Pio/RA were maintained under 12h-light12h-dark conditions. RC3 and GAP-43 mRNA levels were determined by RT-PCR. Lipid peroxidation and protein carbonyls levels were determined by colorimetric assays. Aβ protein levels were analyzed by immunoblotting. We found that Pio/RA reestablished rhythmicity of those temporal patterns. These findings might constitute, at least in part, molecular and biochemical basis of restoration of circadian rhythmicity by the administration of Pio/RA in neurodegenerative disorders.