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In a major boost to Australia before the tour of the British and Irish Lions in June and July, the lock will skipper the 2011 Super Rugby champions against South Africa's Bulls at Lang Park in Brisbane on Saturday.
Horwill, who sustained a hamstring injury in a freak incident in a match against ACT Brumbies last May, had been slated to return in the pre-season in early February but injured himself in the final training session before the match.
"Getting James back on the field has been a long time coming and everyone is extremely excited to see him back after what has been a frustrating 10 months without rugby," Reds coach Ewen McKenzie said in a news release.
"In a perfect world he would have returned sooner if not for an ankle injury he suffered in an unlucky instance at training, but he has handled every challenge thrown at him with class and is now ready to go."
Nicknamed "Big Kev" after the enthusiastic star of a popular Australian TV commercial, Horwill missed the entire international season last year after leading the Wallabies to the World Cup in 2011.
A long run in the Reds side for Horwill would be welcome to Australia coach Robbie Deans, and not just because of the 27-year-old's leadership capabilities.
Australia, who are likely to be sorely tested by the Lions up front, suffer from a serious lack of depth in the second row and lost 116-cap lock Nathan Sharpe to retirement at the end of last season.
Horwill makes his return a week after influential Wallabies and Reds scrumhalf Will Genia, who had been sidelined by knee reconstruction and played in the Reds' shock defeat to the Perth-based Western Force last weekend.
Reds openside flanker Liam Gill, promoted to second in the Wallabies pecking order behind Michael Hooper by the season-ending injury to David Pocock, will miss Saturday's match against the Bulls because of a knee injury, however.
"While we don't consider his injury severe, it's too early in the season to risk putting him out there and ultimately suffering further damage," said McKenzie.
Big-tackling outside centre Anthony Faingaa, another Wallabies regular, also returns after being forced to pull out of last week's match against the Force because of a back injury.
Test winger Digby Ioane is back in the starting line-up after being banned by the Reds for the Force game because of an incident in a Melbourne pub.
