Introduction & Aims: The obesity epidemic is leading to an increase in obesity during pregnancy, which has implications for the health and wellbeing of the offspring. Maternal obesity may influence maternal behaviour which may subsequently affect offspring behaviour and stress responses, however the mechanisms remain unclear. One possibility is that stress responses are mediated by an inflammatory response to a high fat obesogenic diet. To test this hypothesis, this study investigated stress markers involved in hypothalamus-pituitary-adrenal (HPA) axis function, and neuroinflammation in offspring from high-fat (HF)-fed obese mothers, with or without subsequent postnatal HF-feeding, and measures of early maternal and pup behaviour. Methods: Female C57BL/6 mice were fed either a high fat diet (HF; 45% kcal fat) or control diet (C; 7% kcal fat) 6 weeks before mating, throughout pregnancy and lactation. Weaned offspring were fed C or HF diet resulting in 4 offspring groups: C/C (n=5), C/HF (n=4), HF/C (n=6), HF/HF (n=4) (pre/postnatal diet). In 15 week-old male offspring brain, gene markers of inflammation (IL-1β, TNF-α, FCγR1) and HPA function (corticotropin releasing hormone [CRH], glucocorticoid receptor [GR]) were measured by RT-PCR in the hypothalamic paraventricular nucleus (PVN). In 7 day-old male and female pups (C, n=20; HF, n=6) anxiety was assessed by ultrasonic vocalisation (USV) frequency during 4 min isolation from the dam. Maternal behaviour (C, n=44; HF, n=8) was assessed by recording times of first dam-pup interaction and pup retrieval to the nest in the 2 min following pup return. Data analysis: 2-way ANOVA and t test. Results: IL-1β but not TNF-α was significantly increased (p<0.01) and GR was significantly decreased (p<0.05) in HF-fed male offspring PVN, but only when their mothers were HF-fed (HF/HF). Maternal HF diet also increased CRH and decreased FCγR1 in offspring PVN, regardless of postnatal diet (p<0.05). Pup USV was not different between C and HF pups. The time taken to interact with pups and then return them to the nest was significantly (p<0.0001) longer for HF-fed dams. Conclusions: These results suggest that changes in markers of both neuroinflammation and stress are altered in young adult offspring from obese mothers, but only when fed a HF postnatal diet. Although pup anxiety appeared unaffected by maternal HF-feeding, the reduction in mother-to-pup interaction at postnatal day 7 may have longer-term effects on stress responses and behaviour in HF offspring. Further studies of behaviour of these offspring later in their lifespan will determine whether potential behavioural changes, including anxiety and memory and learning, can be specifically linked to altered hypothalamic inflammatory and stress markers.