Barker had long appreciated the literary figures she draws inspiration from in the novel: she read the World War I poetry of Sassoon and Owen as well as Rivers' Conflict and Dream in her youth. However, Barker directly attributes the immediate inspiration for Regeneration to her husband, a neurologist familiar with the writings of Dr. W.H.R. Rivers and his experiments with nerve regeneration. In a 2004 interview with literary critic Rob Nixon in the journal Contemporary Literature, Barker also states she wrote the novel, in part, as a response to how her earlier fiction was being received; she said,
I felt I had got myself into a box where I was strongly typecast as a northern, regional, working-class, feminist—label, label, label—novelist. It's not a matter so much of objecting to the labels, but you do get to a point where people are reading the labels instead of the book. And I felt I'd got to that point. And also, I'd always wanted to write about the First World War. One of my earliest memories was of my grandfather's bayonet wound and his stories of the First World War. I knew I wanted to do that. I also knew I had to wait until I'd got a way of doing it that wasn't just a copy of what had already been done. It takes a long time to have an original idea about something which has got whole libraries devoted to it.
Other interviews also emphasise her memories of her grandfather's stories about his experience.
In her "Author's Note" for the novel, she describes the research which she used to create the novel, and how she drew on a number of sources from different period authors. The novel draws considerable inspiration from historical events. Literary critic Greg Harris describes her use of historical circumstances and historical source materials as largely, " "true" to the extent that the lives of the real-life characters, including Wilfred Owen, Siegfried Sassoon, and Robert Graves, did intertwine." Moreover, Harris argues that Barker accurately captures the psychological situation in which the characters, especially the literary characters, were producing their poetry. French literary critic Marie-Noëlle Provost-Vallet highlights different misinterpretations and anachronistic cultural references supporting a critique of the novel by blogger and critic Esther MacCallum-Stewart. However, she also notes the novel accurately assesses other parts of the historical context, such as the treatment of the World War I poets' and their poetic process.