Circadian rhythms refer to endogenous biological oscillations with a 24-hour periodicity which are directly under the control of the core clock located within the hypothalamus. The disruption of said circadian rhythms via rotational or night-shift work has been linked to the development of metabolic diseases such as obesity and type 2 diabetes (T2D). The specific contributions of the core clock to this dysregulation have been elucidated following the development of tissue-specific knockout mice. For example, both skeletal muscle and hepatic-specific CLOCK and BMAL1 knockout mice display impairments in glucose control [1 2]. Despite this, evidence of circadian disruption in more physiological models of T2D is limited. In particular, although the use of diet-induced models is common, these models tend not to develop hyperglycaemia and overt T2D. Therefore, we have utilised the TallyHO/Jng mouse (JAX stock #005314) as a model of T2D. Interestingly, the development of the hyperglycaemic phenotype within this strain is not 100% penetrant which allows us the segregate the mice into two divergent strains of normoglycaemic (Tally-Low) and hyperglycaemic (Tally-High) TallyHO/Jng mice. The SWR/J mouse (JAX stock #000689) strain was utilised as the recommended healthy control. Therefore, our aim was to characterise the development of the diabetic phenotype in Tally-Low and Tally-High mice in comparison to SWR/J mice. In addition, we aimed to determine how hyperglycaemia influences the expression of circadian clock genes across the circadian cycle. Body weight and blood glucose was monitored on a weekly basis from 8 to 16 weeks of age (n=8/group). Plasma insulin was determined at 8 and 16 weeks of age (n=8/group). At 16 weeks of age, SWR/J, Tally-Low and Tally-High (n=6/group) mice were anaesthetized (50 mg pentobarbital/kg BW) and sacrificed via cervical dislocation at ZT3 (9am) and ZT15 (9 pm) and tissue samples collected. Skeletal muscle circadian clock related gene expression was assessed via RT-qPCR and protein levels via immunoblotting. Data were analysed via two-way ANOVA with Bonferroni correction and data presented as mean ± standard deviation. All procedures were approved by the Danish Animal Experiments Inspectorate and complied with European Directive 2010/63/EU for animal experiments. Tally-High mice displayed overt hyperglycaemia by 8-weeks of age (19.9 ± 5.2 mmol) in comparison to Tally-Low (8.9 ± 2.2 mmol) and SWR/J (6.7 ± 1.1 mmol) mice (P < 0.05). At 8-weeks of age, both Tally-Low (3.5 ± 1.2 ng/ml) and Tally-High (3.1 ± 1.0 ng/ml) display hyperinsulinemia in comparison to SWR/J mice (0.7 ± 0.3 ng/ml) (P < 0.05). At 16-weeks of age, skeletal muscle Bmal1 expression displayed diurnal rhythmicity between ZT3 and ZT15 in both SWR/J and Tally-Low mice (P 0.05). In conclusion, the divergent phenotype development in the TallyHO/Jng mouse represents an interesting model to study the effects of hyperglycaemia. The exacerbated hyperglycaemia in the Tally-High mice resulted in disrupted diurnal rhythmicity in Bmal1 expression in skeletal muscle. These data suggest that disruptions to the clock machinery in peripheral tissues may contribute to the divergent phenotype development in TallyHO/Jng mice.